Categories: C-N Bond Formation > Amines >
Synthesis of arylamines
Iridium complexes bearing an N-heterocyclic carbene (NHC) ligand exhibited high catalytic performance for the N-methylation of both aliphatic and aromatic primary amines using methanol as the methylating agent. For aliphatic amines, selective N,N-dimethylation was achieved at low temperatures. For aromatic amines, selective N-monomethylation and selective N,N-dimethylation were accomplished.
G. Toyooka, A. Tuji, K.-i. Fujita, Synthesis, 2018, 50, 4617-4626.
A Cp*Ir complex bearing a functional 2,2′-bibenzimidazole ligand is a highly effective and general catalyst for the N-methylation of a variety of amines with methanol in the presence of a weak base.
R. Liang, S. Li, R. Wang, L. Lu, F. Li, Org. Lett., 2017, 19, 5790-5793.
[(p-cymene)Ru(2,2'-bpyO)(H2O)] is a general and efficient catalyst for the N-methylation of amines and sulfonamides with methanol in the presence of a carbonate salt. The reaction tolerates a series of sensitive substituents, such as nitro, ester, cyano, and vinyl groups.
P. Liu, N. T. Tung, X. Xu, J. Yang, F. Li, J. Org. Chem., 2021, 86, 2621-2631.
Various aromatic amines were selectively methylated in the presence of MeOH and KOtBu into their corresponding monomethylated secondary amines in high yields at 150°C with very low loading of a PNHP-Pincer Ru catalyst.
O. Ogata, H. Nara, M. Fujiwhara, K. Matsumura, Y. Kayaki, Org. Lett., 2018, 20, 3866-3870.
A Chan-Lam coupling using methylboronic acid enables a selective monomethylation of anilines. An incubation period of the substrate with the copper reagent is needed before addition of the methylboronic acid. N-Methylanilines are synthesized in good yields.
I. González, J. Mosquera, C. Guerrero, R. Rodríguez, Jacobo Cruces, Org. Lett., 2009, 11, 1677-1680.
A copper-catalyzed protocol for reductive methylation of amines and imine with formic acid as a C1 source and phenylsilane as a reductant provides the corresponding methylamines in good to excellent yields under mild conditions.
C. Qiao, X.-F. Liu, X. Liu, L.-N. He, Org. Lett., 2017, 19, 1490-1493.
An iron(0) complex bearing a cyclopentadienone ligand catalyzes mild N-ethylation and N-methylation of aryl and aliphatic amines with ethanol or methanol in basic conditions through a hydrogen autotransfer borrowing process. A broad range of aromatic and aliphatic amines underwent mono- or dialkylation in high yields.
A. Lator, S. Gaillard, A. Poater, J.-L. Renau, Org. Lett., 2018, 20, 5985-5990.
Well-defined Co(II) complexes stabilized by a PCP ligand catalyze efficient alkylations of aromatic amines by primary alcohols into mono-N-alkylated amines in very good yields. The inexpensive, earth-abundant nonprecious metal catalysts make this acceptorless alcohol dehydrogenation concept environmentally benign.
M. Mastalir, G. Tomsu, E. Pittenauer, G. Allmaier, K. Kirchner, Org. Lett., 2016, 18, 3462-3465.
A radical-mediated decarboxylative C(sp3)-N cross-coupling of diacyl peroxides with nitrogen nucleophiles, including indazoles, triazoles, indoles, and anilines provides a broad range of alkylated products. The primary and secondary alkyl radicals derived from corresponding diacyl peroxides were generated by copper catalysis or by merging copper catalysis and photoredox catalysis, respectively.
Z. -L. Tang, X.-H. Ouyang, R.-J. Song, J.-H. Li, Org. Lett., 2021, 23, 1000-1004.
At atmospheric pressure and at 130-160°C, primary aromatic amines are mono-N-alkylated with a very high selectivity in a single step, with symmetrical and asymmetrical dialkyl carbonates in the presence of a commercially available NaY faujasite. No solvents are required.
M. Selva, P. Tundo, A. Perosa, J. Org. Chem., 2001, 66, 677-680.
In the presence of a catalytic amount of copper(II) acetate and di-tert-butyl peroxide, a cross-coupling reaction of anilines with alkylborane reagents gives N-alkylated anilines in good to excellent yields. Phenols are also applicable for this reaction.
S. Sueki, Y. Kuninobu, Org. Lett., 2013, 15, 1544-1547.
An easy Pd-mediated oxidation of primary amines to imines followed by aniline addition enables an alkylation of anilines. The process is characterized by a high atom economy as ammonia is the only byproduct. The catalyst could be successfully recycled up to three times.
P. Linciano, M. Pizzetti, A. Porcheddu, M. Taddei, Synlett, 2013, 24, 2249-2254.
A catalytic system generated in situ from a tetranuclear Ru-H complex with a catechol ligand enables a direct deaminative coupling of two primary amines to form secondary amines. The analogous coupling of aniline with primary amines formed aryl-substituted secondary amines.
P. T. K. Arachchige, H. Lee, C. S. Yi, J. Org. Chem., 2018, 83, 4932-4947.
A catalytic amount of CuCl was used in combination with 4CzIPN as organic photoredox catalyst to effect decarboxylative C(sp3)-N coupling. The reaction provides a variety of alkyl amines from readily available alkyl carboxylic acids. The coupling worked with both anilines and imines as nitrogen sources.
G. Barzanň, R. Mao, M. Garreau, J. Waser, X. Hu, Org. Lett., 2020, 22, 5412-5416.
Commercially available [(PPh3)2NiCl2] is an efficient catalyst for the mono-N-alkylation of (hetero)aromatic amines, employing alcohols to deliver diverse secondary amines in excellent yields via the borrowing hydrogen strategy. The catalyst system can also be used for accessing various quinoline derivatives following the acceptorless dehydrogenation pathway.
S. N. R. Donthireddy, V. K. Pandey, A. Rit, J. Org. Chem., 2021, 86, 6994-7001.
A monobenzylation of aromatic amines with benzylic alcohols in good yields proceeds under MW conditions in the presence of SmI2 as a catalyst with the generation of water as the sole byproduct. This reaction offers a broad substrate scope and good functional-group tolerance.
J. Gour, S. Gatadi, S. Malasala, M. V. Yaddanpudi, S. Nanduri, J. Org. Chem., 2019, 84, 7488-7494.
A base-catalyzed/promoted transition-metal-free direct alkylation of amines with either aromatic or aliphatic alcohols provides the desired amines in good yields.
Q.-Q. Li, Z.-F. Xiao, C.-Z. Yao, H.-X. Zheng, Y.-B. Kang, Org. Lett., 2015, 17, 5328-5331.
The addition of 4 Ĺ molecular sieves enables an efficient cobalt(II)-catalyzed N-alkylation of both aromatic and aliphatic amines with alcohols with high chemoselectivity (amines vs imines). A hydrogen-borrowing mechanism is responsible for the tandem acceptorless dehydrogenation/condensation/hydrogenation process.
G. Zhang, Z. Yin, S. Zheng, Org. Lett., 2016, 18, 300-303.
Copper N-heterocyclic carbene complexes serve as catalysts for both aerobic oxidation of alcohols to aldehydes and reduction of imines to amines. A one-pot tandem synthetic strategy affords useful secondary amines from benzylic alcohols and anilines via an oxidation-reduction strategy.
L.-W. Zhan, L. Han, P. Xing, B. Jiang, Org. Lett., 2015, 17, 5990-5993.
The [RuCl2(p-cymene)]2/Ph2SiH2 catalytic system is very efficient for the reductive amination of aldehydes with anilines to provide secondary amines and tertiary amines in good yields. The method is highly chemoselective and tolerates a wide range of functional groups, such as NO2, CN, CO2Me, F, Cl, Br, OMe, Me, furyl and alkyl.
B. Li, J. Zheng, W. Zeng, Y. Li, L. Chen, Synthesis, 2017, 49, 1349-1355.
A Chan-Lam coupling reaction of benzylic and allylic boronic esters with primary and secondary anilines provides valuable alkyl amine products. Both secondary and tertiary boronic esters can be used as coupling partners, with mono-alkylation of the aniline occurring selectively.
J. D. Grayson, F. M. Dennis, C. C. Robertson, B. M. Partridge, J. Org. Chem., 2021, 86, 9883-9897.
Dibutyltin dichloride catalyzes a direct reductive amination of aldehydes and ketones in the presence of phenylsilane as a stoichiometric reductant. Suitable amines included anilines and dialkylamines but not monoalkylamines.
R. Apodaca, W. Xiao, Org. Lett., 2001, 3, 1745-1748.
A simple copper-promoted N-monoalkylation of anilines that utilizes alkyl boronic acids as the alkylating partner is carried out in refluxing dioxane and allows a number of structurally and electronically diverse anilines to be functionalized in a single step. A broad study was carried out to demonstrate the utility of this new methodology for the preparation of phenethylanilines.
M. Larrosa, C. Guerrero, R. Rodríguez, J. Cruces, Synlett, 2010, 2101-2105.
A CuI-based catalytic system in combination with an easily accessible prolinamide ligand enables an Ullmann-type cross coupling of a variety of aromatic, aliphatic amines with aryl halides in aqueous media. The method is mild and tolerates air and a wide range of functional groups. Secondary amines like heteroaromatic amines and nucleobases afford the corresponding coupling products in good to excellent yields too.
G. Chakraborti, S. Paladhi, T. Mandal, J. Dash, J. Org. Chem., 2018, 83, 7347-7359.
The use of in situ generated magnesium amides in the presence of a lithium halide dramatically increases the product yield of iron-catalyzed amination reactions. The present method is simple and free of precious and expensive metals and ligands and provides a convenient route to triarylamines, a recurrent core unit in organic electronic materials as well as pharmaceuticals.
T. Hatakeyama, R. Imayoshi, Y. Yoshimoto, S. K. Ghorai, M. Jin, H. Takaya, K. Norisuye, Y. Sohrin, M. Nakamura, J. Am. Chem. Soc., 2012, 134, 20262-20265.
In the presence of N,N,N′,N′-tetramethylethylenediamine (TMEDA) as an additive, easily prepared and handled N-chloroamines react with aryl Grignard reagents to give various arylamines in good to excellent yields. Functional groups such as ester and nitrile are tolerated.
T. Hatakeyama, Y. Yoshimoto, S. K. Ghorai, M. Nakamura, Org. Lett., 2010, 12, 1516-1519.
A rhodium-catalyzed amination reaction of aryl halides with amines takes place in the presence of a N-heterocyclic carbene ligand. The active metal species responsible for the reaction progress was identified. This convenient and mild procedure for Rh-catalyzed N-arylation displays a wide range of substrate scope and high degree of functional group tolerance.
M. Kim, S. Chang, Org. Lett., 2010, 12, 1640-1643.
A transition-metal-free synthesis of aryl- and heteroarylamines employs a small-ring organophosphorus-based catalyst and a terminal hydrosilane reductant to drive reductive intermolecular coupling of nitroarenes with boronic acids. Applications to the construction of both Csp2-N (from arylboronic acids) and Csp3-N bonds (from alkylboronic acids) are demonstrated; the reaction is stereospecific with respect to Csp3-N bond formation.
T. V. Nykaza, J. C. Cooper, G. Li, N. Mahieu, A. Ramirez, M. R. Luzung, A. T. Radosevich, J. Am. Chem. Soc., 2018, 140, 15200-15205.
A low-valent tungsten complex catalyzes a visible light mediated amination of boronic acids with nitroaromatics at ambient temperature. With readily available W(CO)6 as a precatalyst under external-photosensitizer-free conditions, nitroaromatics smoothly undergo C-N coupling reactions with boronic acids, delivering structurally diverse secondary amines in good yields.
H. Song, Y. Shen, H. Zhou, D. Ding, F. Yang, Y. Wang, C. Xu, X. Cai, J. Org. Chem., 2022, 87, 5303-5314.
Palladium/N-heterocyclic carbene (NHC) catalysis achieves an amination of diaryl sulfoxides with anilines and alkylamines. This amination tolerates a wide range of functional groups such as silyl, boryl, methylsulfanyl, and halogen moieties. Regioselective amination of unsymmetrical diaryl sulfoxides was also executed by means of steric bias.
Y. Yoshida, S. Otsuka, K. Nogi, H. Yorimitsu, Org. Lett., 2018, 20, 1134-1137.
Various aromatic amines expediently underwent a copper-catalyzed N-tert-butylation in the presence of tert-butyl 2,2,2-trichloroacetimidate at room temperature.
J. W. Cran, D. V. Vidhani, M. E. Krafft, Synlett, 2014, 25, 1550-1554.
The sequential combination of Ti-catalyzed hydroamination of alkynes followed by the Ti-catalyzed hydrosilylation of the intermediate imines is an efficient one-pot process for the conversion of alkynes and primary amines into secondary amines.
A. Heutling, F. Pohlki, I. Bytschkov, S. Doye, Angew. Chem. Int. Ed., 2005, 44, 2951-2954.
1,2,3-triazole-bound cationic Au(I) catalysts possess much better thermal stability than literature-reported Au catalysts, including IPrAu•NTf2. By application of these catalysts, challenging intermolecular hydroaminations were achieved with less-reactive internal alkynes and unprotected aliphatic amines, giving excellent yields with low catalyst loading.
H. Duan, S. Sengupta, J. L. Petersen, N. G. Akhmedov, X. Shi, J. Am. Chem. Soc., 2009, 131, 12100-12102.
An efficient intermolecular hydroamination of unactivated alkenes with anilines catalyzed by lanthanide salts gives Markovnikov products in good yields.
P. Yin, T.-P. Loh, Org. Lett., 2009, 11, 3791-3793.
N-Alkylaminobenzenes were prepared in a simple and efficient one-pot synthesis by reduction of nitrobenzenes followed by reductive amination with decaborane (B10H14) in the presence of 10% Pd/C.
J. W. Bae, Y. J. Cho, S. H. Lee, C.-O. M. Yoon, C. M. Yoon, Chem. Commun., 2000, 1857-1858.
Cooperative catalysis of an Ir(III)-diamine complex and a chiral phosphoric acid or its conjugate base enables a direct reductive amination of a wide range of ketones.
C. Li, B. Villa-Marcos, J. Xiao, J. Am. Chem. Soc., 2009, 131, 6967-6969.
The NiCl2(PPh3)2-PPh3-catalyzed cross-coupling of bromomagnesium diarylamides, generated in situ from diarylamines, with aryl bromides or iodides is an inexpensive, convenient, and practical method for the synthesis of triarylamines.
C. Chen, L.-M. Yang, Org. Lett., 2005, 7, 2209-2211.
Air- and moisture-stable Ni(II)-(σ-aryl) complexes, associated with N-heterocyclic carbene ligands, produce a catalytically active Ni(0) species in situ for an efficient amination of aryl chlorides with anilines and secondary cyclic amines under mild conditions.
C. Chen, L-M. Yang, J. Org. Chem., 2007, 72, 6324-6327.
A base-mediated hydroamination protocol with substoichiometric amounts of a hydrosilane and potassium tert-butoxide operates under mild conditions. Many aryl- and heteroatom-substituted olefins as well as arylamines are tolerated, affording the desired products with complete regioselectivity.
P. Li, B. C. Lee, X. Zhang, M. J. Koh, Synthesis, 2022, 54, 1566-1576.
A cobalt-catalyzed highly branched- and enantioselective allylic amination of racemic branched allylic carbonates bearing alkyl groups with both aromatic and aliphatic amines provides allylic amines in high yields with exclusively branched selectivity and excellent enantioselectivities under mild reaction conditions.
S. Ghorai, S. S. Chirke, W.-B. Xu, J.-F. Chen, C. Li, J. Am. Chem. Soc., 2019, 141, 11430-11434.
A rhodium-catalyzed regioselective amination of secondary allylic trichloroacetimidates with unactivated aromatic amines gives N-arylamines in high yields and regioselectivity, favoring the branched amination products. The presence of the trichloroacetimidate leaving group was found to be critical for successful regioselective amination reactions with unactivated aromatic amines.
J. S. Arnold, R. F. Stone, H. M. Nguyen, Org. Lett., 2010, 12, 4580-4583.
A ligand-free copper-catalyzed hydroamination of allenes with cyclic secondary amines or anilines derivatives provides (E)-allylamines under smooth conditions with total regio- and stereoselectivity.
R. Blieck, J. Bahri, M. Taillefer, F. Monnier, Org. Lett., 2016, 18, 1482-1485.
A rhodium-catalyzed regioselective amination of tertiary allylic trichloroacetimidates with unactivated aromatic amines is a direct and efficient approach to the preparation of α,α-disubstituted allylic aryl amines in good yield and with excellent regioselectivity. This method enables the conversion of unactivated primary and secondary amines and the preparation of reverse prenylated indoles in two steps.
J. S. Arnold, G. T. Cizio, H. M. Nguyen, Org. Lett., 2011, 13, 5576-5579.
Various allyl carbonates have been converted under Fe catalysis into essentially regio- and stereoisomerically pure allyl amines. Catalytic amounts of piperidinium hydrochloride as a buffer retard catalyst decomposition.
B. Plietker, Angew. Chem. Int. Ed., 2006, 45, 6053-6056.
p-Toluenesulfonic acid efficiently catalyzes direct nucleophilic substitutions of the hydroxy groups of propargylic alcohols with a large variety of carbon- and heteroatom-centered nucleophiles. Reactions can be conducted under mild conditions and in air without the need for dried solvents.
R. Sanz, A. Martinez, J. M. Alvarez-Gutierrez, F. Rodriquez, Eur. J. Org. Chem., 2006, 1383-1386.
A direct Fe-catalyzed synthesis of β-alkyl N-aryl aza Baylis-Hillman (ABH) adducts involves the formation of a C–N bond via a nitroso-ene reaction. This is a simple, fast, and best alternate method to overcome the substrate scope limitations of the ABH reaction. Various arylhydroxylamines reacted with esters, aldehydes, ketone, and nitriles to yield the corresponding products in good yields.
S. Murru, A. A. Gallo, R. S. Srivastava, J. Org. Chem., 2012, 77, 7119-7123.
A palladium-catalyzed allylic amination enables an asymmetric synthesis of α,α-disubstituted allylic N-arylamines from highly modular vinyl cyclic carbonates and unactivated aromatic amine nucleophiles. The catalytic process features minimal waste production, high asymmetric induction, and operational simplicity.
A. Cai, W. Guo, L. Martínez-Rodríguez, A. W. Kleij, J. Am. Chem. Soc., 2016, 138, 14194-14197.
A regio- and enantioselective amination of racemic tertiary allylic trichloroacetimidates with a variety of aniline nucleophiles in the presence of a chiral diene-ligated rhodium catalyst is a direct and efficient route to chiral α,α-disubstituted allylic N-arylamines in good yields with very good levels of regio- and enantioselectivity.
J. S. Arnold, H. M. Nguyen, J. Am. Chem. Soc., 2012, 134, 8380-8383.
An efficient and very simple conjugate addition of aromatic and aliphatic amines to α,β-unsaturated carbonyl compounds under solvent-free conditions in the presence of catalytic amount of silicon tetrachloride gave the corresponding Michael adducts with very good yields.
N. Azizi, R. Baghi, H. Ghafuri, M. Boloutchian, M. Hashemi, Synlett, 2010, 379-382.
Heating a solution of an aldehyde, an aromatic amine, and a nitroalkane in 20% water-methanol at 60 °C for five hours enables an environmentally three-component, one-pot synthesis of 2-nitroamines in the absence of a catalyst.
C. G. Piscopo, G. Sartori, J. A. Mayoral, D. Lanari, L. Vaccaro, R. Maggi, Synlett, 2013, 24, 2596-2600.